Additional Patients at Increased Risk for SJS/TEN With Urate-Lowering Drugs

An increased risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) after urate-lowering therapy was found not only in Asians but also in blacks, according to research published in Seminars in Arthritis & Rheumatism.  

The American College of Rheumatology currently recommends screening for the human leukocyte antigen (HLA)-B*5801 allele prior to initiation of urate-lowering therapy in at-risk patient populations, including Han Chinese and Koreans. This study is the first to suggest that black patients may also benefit from screening. Prior studies have linked HLA-B*5801 with allopurinol hypersensitivity syndrome, and US population frequencies of the allele are consistent with these new findings. 

“Given its market dominance and established association with SJS/TEN, our findings support the use of vigilance in these minorities when considering allopurinol,” the authors of the study wrote.

Hyon K. Choi, MD, DrPH, of Harvard Medical School and Massachusetts General Hospital in Boston, and colleagues, designed a study to evaluate whether the risk of SJS and TEN associated with urate-lowering pharmacotherapy varied in the U.S. population. 

Using 2009–2013 data from the Nationwide Inpatient Sample of the Agency for Healthcare Research and Quality, the study authors examined 606 patients hospitalized with a principal discharge diagnoses of SJS or TEN, in combination with a secondary discharge diagnoses of adverse effects due to uric acid metabolism therapy.

In the patients examined, there was a greater representation of Asian and black patients as compared to white patients. Black patients made up 13% of allopurinol users but 26% of hospitalizations for SJS or TEN. 

Hospitalization rate ratios for SJS/TEN was 11.9% among Asian patients included in the sample study, was 5.0% for blacks, and was 1.0% for whites (referent). These associations persisted using other national referents. 

Summary and Clinical Applicability

“These national data indicate that Asians and blacks have a substantially higher risk of SJS/TEN as [urate-lowering drug adverse effects] than whites (or Hispanics), correlating well with corresponding frequencies of HLA-B*5801 in the US population”, the authors concluded.

Limitations and Disclosures

This study was limited by the lack of information on specific doses of urate-lowering drugs utilized and the use of a national administrative database to collect clinical information on patients. 

Several co-authors of this study have disclosed financial relationships with Takeda, AstraZeneca, Pfizer, Lilly, and Genentech.

Reference

Lu N, Rai SK, Turkeltaub R, et al. Racial disparities in the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis as urate-lowering drug adverse events in the U.S. Semin Arthritis Rheum 2016; DOI: 10.1016/j.semarthrit.2016.03.014.